Total syntheses of the immunosuppressants SNF4435 C and D as well as the antibiotics spectinabilin and N-acetyl aureothamine are proposed. These highly unsaturated polypropionates were isolated from various strains of Streptomyces sp. Furthermore, synthetic approaches towards the molluscan polypropionates photodeoxytridachione and crispatene as well as the fungal immunosuppressants candelalide A and B are presented. All natural products feature a terminal gamma-pyrone moiety as a common structural motif. Polyenes consisting of an array of conjugated trisubstituted double bonds have been used as synthetic precursors of the complex polypropionates. The stereoselective assembly of these structures will be further investigated. Preliminary studies have shown that the core bicyclo[4.2.0]octadiene core of SNF4435 compounds can be formed using a highly stereoselective tandem Stille cross-coupling / electrocyclization cascade. A novel Lewis-acid catalyzed cyclization leading to the bicyclo[3.1.0]hexane core of photodeoxytridachione and crispatene has also been developed. The proposed total syntheses provide an opportunity to investigate asymmetric electrocyclization reactions. As opposed to cycloadditions and sigmatropic rearrangements, this class of pericyclic reactions has not yet succumbed to asymmetric catalysis. In a further contribution to synthetic methodology, new approaches towards gamma-pyrones are proposed. The significance of the gamma-pyrone moiety for the biological activity of the natural products will be explored. The biological mode of action of SNF4435C and D remains presently unknown. The natural products do not suppress IL-2 production, distinguishing them from FK506 or cyclosporin A. Our synthetic material and derivatives thereof will be used to isolate binding proteins and gain further insight into of the mechanism of these promising new lead compounds for drug development.